The molecular biology mechanism of cardiomyopathy in aging and metabolic disease: the effects of probiotics supplement therapy in diabetes mellitus and resveratrol combined exercise prescription in aging

• Main Authors: Chih-Hsueh Lin, 林志學
• Other Authors: Cheng-Chieh Lin
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/hb8fet

博士 === 中國醫藥大學 === 老化醫學博士學位學程 === 102 === The definition of aging from World Health Organization is 65 year old with a character of physical decline. In prediction, the over 65 year aged people is more than 2 million and over 11% of whole population in Taiwan in 2013. Moreover, the risks of cardiomyopathy and diabetes mellitus (DM) are increasing with the age in elder people. Coronary heart disease (CHD) and diabetic cardiomyopathy (DC) in particular is a major cause of morbidity and mortality associated with diabetes. According to previous reports, diabetic patients have a 5-fold increased risk of CHD. Probiotics are widely known to demonstrate various beneficial effects on potential pharmaceutical applications. Probiotics in the prevention and treatment of metabolic disorders, including obesity, blood sugar and improve bowel function improvement, have many positive results. Resveratrol is a plant polyphenolic compounds and many recent studies point to its benefits for human health, including lowering blood sugar, improving insulin resistance, regulating lipid metabolism, anti-aging, and anti-oxidation effects. There were two objectives in the present study. First was to evaluate whether oral Lactobacillus reuteri GMN-32 treatment reduces blood glucose concentrations and promotes cardiac function in rats with streptozotocin-induced DM. The other objective was to evaluate whether resveratrol enhanced FOXO3 phosphorylation via synergetic activate SIRT-1 and PI3K/Akt signaling to benefit exercise effects in elderly rat hearts. The first study, we separated into four groups. Group I consisted of control rats, group II consisted of Streptozocin-induced DM rats, and groups III and IV consisted of Streptozocin-induced DM rats treated with lower (107 cfu/ml /per d) and high (109 cfu/ml per d) of L. reuteri GMN-32, respectively. The blood glucose levels of the Streptozocin-induced DM rats when treated with L. reuteri GMN-32 decreased from 4480 to 3620 mg/l in lower group and 3040 mg/l in high group. Probiotics treatment also reduced the changes in the heart caused by the effects of DM. Furthermore, the Fas/Fas -associated protein with death domain pathway-induced caspase 8-mediated apoptosis that was observed in the cardiomyocytes of the Streptozocin-induced DM rats was also found to be controlled in the probiotics-treated rats. The results highlighted that L. reuteri GMN-32 treatment reduced blood glucose levels, inhibited caspase 8-mediated apoptosis and promoted cardiac function in DM rats as observed from their ejection fraction and fractional shortening values. The other study, 18-month aged old rats were used as the experimental model, and give them individually with swimming exercise training, resveratrol treatment (15mg/kg/day) and exercise training co-treated with resveratrol for 4 weeks. The results showed the heart function of each group rat heart was promoted. However, our old rats with swimming exercise cause slightly inevitable impact of cell apoptosis and fibrosis phenomena. In protein analysis, the PI3K-Akt pathway is slightly increased in exercise training and resveratrol treatment, but Sirt-1was only highly activated in resveratrol treatment group. Moreover, the exercise training co-treated with resveratrol provided the benefits from Sirt-1 and PI3K-Akt dual pathways and blocked the FOXO3 accumulation. Our experimental results suggested that resveratrol treatment warrants the beneficial effects of exercise training in aging rat hearts. In conclusion, the administration of L. reuteri GMN-32 probiotics can regulate blood glucose levels, protect cardiomyocytes and prevent DC in DM rats. Resveratrol supplement had therapeutic effect on heart protection in the exercise training for aging. Future studies should be using probiotics as adjuvant therapy in DM patients to reduce blood sugar fluctuations and prevent cardiomyopathy and resveratrol protects the heart functions for the elderly when exercise.